Genetically predicted body mass index and Alzheimer's disease–related phenotypes in three large samples: Mendelian randomization analyses
Abstract
Observational research shows that higher body mass index (BMI) increases Alzheimer's disease (AD) risk, but it is unclear whether this association is causal. We applied genetic variants that predict BMI in Mendelian randomization analyses, an approach that is not biased by reverse causation or confounding, to evaluate whether higher BMI increases AD risk. We evaluated individual‐level data from the AD Genetics Consortium (ADGC: 10,079 AD cases and 9613 controls), the Health and Retirement Study (HRS: 8403 participants with algorithm‐predicted dementia status), and published associations from the Genetic and Environmental Risk for AD consortium (GERAD1: 3177 AD cases and 7277 controls). No evidence from individual single‐nucleotide polymorphisms or polygenic scores indicated BMI increased AD risk. Mendelian randomization effect estimates per BMI point (95% confidence intervals) were as follows: ADGC, odds ratio (OR) = 0.95 (0.90–1.01); HRS, OR = 1.00 (0.75–1.32); GERAD1, OR = 0.96 (0.87–1.07). One subscore (cellular processes not otherwise specified) unexpectedly predicted lower AD risk.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jun 13, 2015
- Source ID
- 10.1016/j.jalz.2015.05.015
Entities
People
- Adult Changes In Thought Study Investigators
- Alzheimer's Disease Genetics Consortium
- Andrew J. Saykin
- David A. Bennett
- Eric B. Larson
- John S.k. Kauwe
- M. Maria Glymour
- Paul K. Crane
- Religious Orders Study/memory And Aging Project Investigators
- Shubhabrata Mukherjee
- Stefan Walter
Organizations
- Alzheimer's Research UK
- BRACE
- Boston University
- Brigham Young University
- Canadian Institutes of Health Research
- Columbia University
- Crohn's and Colitis UK
- Duke University
- Emory University
- GSK
- Howard Hughes Medical Institute
- Indiana University
- Johns Hopkins University
- Kaiser Permanente Washington Health Research Institute
- Massachusetts General Hospital
- Mayo Clinic
- National Institute of Biomedical Imaging and Bioengineering
- National Institute of Neurological Disorders and Stroke
- National Institute on Aging
- National Institutes of Health
- New York University
- Newcastle University
- Northwestern University
- Rush University
- Stichting MS Research
- United States Department of Defense
- University of Alabama at Birmingham
- University of Arizona
- University of Barcelona
- University of California, Davis
- University of California, Irvine
- University of California, Los Angeles
- University of California, San Diego
- University of California, San Francisco
- University of Kentucky
- University of Miami
- University of Michigan
- University of Pennsylvania
- University of Pittsburgh
- University of Southern California
- University of Washington
- Vanderbilt University